The term alkaline phosphatase (EC3.1.3.1), abbreviated ALP, groups together a set of enzymes which, at alkaline pH, catalyze the hydrolysis of phosphoric esters.
ALP is present in the cell membranes and is found in the majority of the tissues of the body. Depending on where they are located, they will be referred to as intestinal, renal, osseous, hepatic, placental and fetal intestinal enzymes. ALP also circulate in the blood serum.
In the human body, four different genes control the expression of ALP: a non-specific tissual gene (coding for the osseous, hepatic and renal isoenzymes in particular), an intestinal gene, a placental gene and a fetal intestinal gene, each of these genes coding for a corresponding isoenzyme.
Each of these isoenzymes may undergo one or more post-translational modifications changing its physicochemical properties but preserving its biological properties and become an isoform
The following isoforms are currently known: isoenzyme bound to an immunoglobulin, tetramer isoenzyme, isoenzyme having an abnormal sialic acid content, isoenzyme bound to cell membrane debris (termed macromolecular) and isoenzyme bound to a lipoprotein, for example to LpX.
The number and the amount of the various isoenzymes and isoforms of alkaline phosphatase vary very substantially depending, on the one hand, on the age and, on the other hand, on the state of health of the individuals.
The osseous and hepatic isoenzymes have been studied in particular because any primary or secondary pathology affecting the osseous and/or hepato-biliary systems is capable of causing an increase or a reduction, depending on the case, in the osseous and/or hepatic isoenzymes in the blood serum and of being accompanied by the appearance of another isoenzyme or of one or more isoforms.
It is known that the level of serum osseous isoenzymes decreases from childhood to adulthood and shows peaks at the time of surges in growth. If a child ceases to grow this is marked by an abnormal reduction in the level of osseous isoenzymes. Surges in growth are accompanied by the presence, in the blood serum, of a second osseous fraction which appears in the form of tetramers.
This fraction is absent from the serum of a normal adult, but it will be discovered if a pathological multiplication process is present in the bones (Paget's disease, osseous metastases, and the like).
An osteoclastic activity will be characterized by the presence of osseous isoenzyme having a lower sialic acid content.
The hepatic isoenzyme normally remains at a constant level throughout the life of an individual in good health.
Degenerative diseases of the liver such as fibrosis and diseases causing a hepatic infiltration and resulting in a progressive destruction of the hepatocytes result in a reduction and then in a disappearance of the hepatic isoenzyme.
An intrahepatic or extrahepatic cholostasis (hepatitis, cirrhosis, hepatic metastases and hepatic compression caused by a tumor in the vicinity, for example) may, on the other hand, cause an increase in the hepatic isoenzyme accompanied by the appearance of the isoform termed macromolecular fraction, hepato-biliary isoform or alpha 1 (bound to a membrane debris) as well as other isoforms, such as the hepatic fractions bound to various lipoproteins.
In the absence of an acute inflammation, the presence of a hepatic isoenzyme having a reduced sialic acid content is a symptom of the presence of tumor.
A hepatic isoenzyme having an abnormal sialic acid content is encountered in infantile transitory hyperphosphatasemia (viral infection of the respiratory or digestive tracts in children).
The identification of other types of isoenzymes of alkaline phosphatase also makes it possible to detect pathological disorders.
Thus, it is known that the presence of placental isoenzymes outside pregnancy is the symptom of a rapidly developing tumor pathology, that intestinal isoenzymes and isoforms in large amounts may be the mark of a systemic disease and that the fetal intestinal isoenzyme is encountered in the case of a primitive liver tumor (hepatoma).
A study of the alkaline phosphatases may therefore provide a substantial aid to diagnosis, but also in monitoring patients in order to follow the development of a disease or to objectify the effect of a treatment.